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      CD209a Synergizes with Dectin-2 and Mincle to Drive Severe Th17 Cell-Mediated Schistosome Egg-Induced Immunopathology

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          SUMMARY

          The immunopathology caused by schistosome helminths varies greatly in humans and among mouse strains. A severe form of parasite egg-induced hepatic granulomatous inflammation, seen in CBA mice, is driven by Th17 cells stimulated by IL-1β and IL-23 produced by dendritic cells that express CD209a (SIGNR5), a C-type lectin receptor (CLR) related to human DC-SIGN. Here, we show that CD209a-deficient CBA mice display decreased Th17 responses and are protected from severe immunopathology. In vitro, CD209a augments the egg-induced IL-1β and IL-23 production initiated by the related CLRs Dectin-2 and Mincle. While Dectin-2 and Mincle trigger an FcRγ-dependent signaling cascade that involves the tyrosine kinase Syk and the trimolecular Card9-Bcl10-Malt1 complex, CD209a promotes the sustained activation of Raf-1. Our findings demonstrate that CD209a drives severe Th17 cell-mediated immunopathology in a helminthic disease based on synergy between DC-SIGN- and Dectin-2-related CLRs.

          In Brief

          Kalantari et al. demonstrate the role of CD209a (SIGNR5) in the development of Th17 cell-mediated immunopathology in murine schistosomiasis. CD209a drives proinflammatory cytokine production in synergy with Dectin-2 and Mincle, each acting via distinct signaling pathways. These findings denote C-type lectin receptor cross talk resulting in severe helminthic disease.

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          Author and article information

          Journal
          101573691
          39703
          Cell Rep
          Cell Rep
          Cell reports
          2211-1247
          9 February 2018
          30 January 2018
          16 February 2018
          : 22
          : 5
          : 1288-1300
          Affiliations
          [1 ]Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA
          [2 ]University of Wisconsin, Microbial Sciences Building, Madison, WI 53706, USA
          [3 ]Institut de Recherches Cliniques de Montreal, Montreal, QC H2W 1R7, Canada
          Author notes
          [4]

          Lead Contact

          Article
          PMC5815841 PMC5815841 5815841 nihpa941221
          10.1016/j.celrep.2018.01.001
          5815841
          29386115
          380dc13d-9482-4b00-a748-f370488b1ae2
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